Apparatus for obtaining aerosols



July 29, 1952 L. DAUTREBANDE APPARATUS FOR OBTAINING AEROSOLS Filed July 27, 1948 m wu u nm TIM l I I WMMWHMWN m un n uu m In 1 H w mm mwwww MW OW ,f. n w i S m 2 N. .n w \u\\-- v z E a m w 1 RM. W. 11! ,1 Q fu 5 N T 1IIMHIIIH, Wm m HHHIIII. W 5 moi Patented July 29, 1952 I I TED STAT-ES 'FSICE '1 APPARATUS .EOR OBTAININGAEBO SOLS Lucien Dautrebande, Washing ton, D. 0., assignor to Aerosol-Corporation of- America, New York, .N.'Y., acorporation of Delaware Application July 27, 1948,1 SerialNo. 40347 4-Claims. (Cl..261-"21) "This invention relates to methods andapparatus for obtaining improved aerosols of-re1ati'vely high stability by "obligatory filtration through aturbulentbody of liquid, and: especially toaerosols of a mean particlesize (diameter) of not over about 0.15 micron.

aerosol therapy, it'is very-important'to-ob- ,tain, aerosols of very:low particle size" if it is desired to have the aerosol penetrate to the innermostpassages or zones in the lungs -(alv eoli). Forthispurposa aerosolsof not over 0.5 micron mean particle size are to be preferred, and in general ';the aerosols should ,be'substantially -'free of. particles oflmore than Imicro-n diameter. The larger aerosol particles attract the smaller ones, theytend to deposit in the nasal and throat passages, andin some'instances su'chdeposit leads either to serious difficulties or toalack of effectiveness of they substances dispersed.

' "In accordance with'the inventiomithasbeen found that aerosols of a'mean particle size of not over 0.5 micron may be ,obtainedreadily by means of a convenient-apparatus.

One of theobjects 'of the invention is to produce improved aerosols having -a mean particle size of not over "0.5 micron. Another object'of the invention is'theprovision of apparatusfor obtaining improved aerosols. Other objects of the invention will beapparent as detailsor embodiments of the-invention are setforth'hereinafter.

accordance with the invention, a liquid is dispersed "by means-0f ai -compressed gas, such as'air, to form ;a cloud containing both stable and unstable dispersed liquid-particle's in the "gas; "and the cloud is'impelled upwardly and passed through a seriesof turbulent bodies of liquid, e. g., three, then- --'directed onto a liquid film layer or baffle, then passedthroug-ha liquid film barrier supported upon an apertured or foraminousmember, and then preferably passed downwardly intoand up through abodyof liquid under agitation. The resulting" aerosol has a mean :particle size of not over "0.5 micron, -e'. g., from an'aqueous solution regardless'o-f' the molecular weight and concentrationof solute'within the usualconcentration ranges suitable for aerosol therapy, e.,g., 1 to 10 y weight of 1. the therapeutioagent. H

--aererrmg-to *the- "drawlng l ig-ure 1- -diagramtheliquid delivery tube 4Q 'voir, which may be det'achably connected;: "by "screw threads, for holding tthe liquideto be dispersed 5, a jet member -made up. of .air inlet "3 and liquid supply tube 4 which extendszinto ;form a continuous-. filrmland thenoutt matically illustrates an apparatus suitable-for tially fragmentary. 1

Figure 2 shows a -cross sectional-view along the lines =2'2 in Figure 1, and shows theathre sets of jet apertures in air inlet =tube in Figure 3 illustrates an alternate aerosol anduit member-=16A; K and alsoah-optitinal bafile at tachment which may be used -with-- fnember- 6 orflSA.

The vessel 1 is provided --with a -liquid :r'eser member 6' having a series -of alternateoiconstriced cross-sectional zones la -suitably i'and preferably adjustably supported substantially vertically over and directly in :the .path 10f lzth'e aerosol cloud formed at zone -2 Member t6 imay be provided with. a detachable funnelshaped ex;- tensioni 6C, if desired. Optional .cylindr'ical screen -member 8 --surrounds..the memberlfi. "irA hood member .1 having a closed top, :apertured sidewall, and =an-enlarged lip lower portion.-isset over and around the :member 66. The lip and suitable support members of :I "fit snugly. in the vessel 1, so that the position. of member :1 may be slidably. adjusted. .Member Y1 dividestvessel ii into an upper zone and a :lo'wer izon'e. Aer'os'o'l delivery tubes l l and M communicate with ves sel I and maylead directly-to an aerosol storage chamber; butypr eferably lead into vessel I 2 near the bottomthereof. Tube 5 cp mctsives eifl z .with theaerosol storagechamber 1-6.

i-If desired,, there maybe provided one orniore optional liquid supply tub'esyla.sand one r "re optional drain ,tubes .11)". iwaterpranothe 11duid may be introduced through .la, and .it'; w'il1 flow-over and down around .me1nber ,-1,..s

1b, .situated :just above the lip portion. -.Qf,- men1- berirl. rMember lrmay becsuitably formedqtsoathat this liquid ,will, not:;f1ow.into ;the.;lo-wer zone; with the upper part gof -':ea.ch-epening:;set wardlygfrom the lower. -part. .L'Ijhe.jopenin'gs:.-- in uid therefrom and replacing it with solution of controlled concentration.

In operation, compressed air or other suitable gas is introduced in tube 3, under such conditions that liquid will be drawn up through tube 4 and dispersed in the form of a cloud or a mist at zone 2 and impelled upwardly into the member 6. The conditions are selected so that the cloud contains both relatively stable and unstable particles, and the latter will condense or deposit in tube 6 and form very turbulent bodies of liquid at the constricted zones thereof. These where unstable liquid particles therein coalesce and form a liquid layer which may flow downwardly along member 8 or the apertured sidewall 'I or both. Then the mist or cloud passes through member 8 and the apertured sidewalls of member I, where unstable liquid particles may coalesce and form continuous liquid layers, into zone I and then through tubes II and I4 into thebody of liquid I3. Under the preferred conditions, the rate of flow of gas is such-that the liquid I3 is maintained under very vigorous agitation thereby- Then. the resulting improved areosols pass through tube I into chamber It.

The apparatus or parts thereof may be made of glass, metal, plastic, or the like suitable material; and although various members are deiscribedas being substantially circular in cross section, othershapes may be used provided the critical relationships disclosed are retained. The member 6 may be made up of sectionsof glass tubing joined by rubber tubing, or all of glass, metal, etc. A two liter Erlenmeyer flask is suitable as vessel I2 in view of its inclined conical wall section. However, for commercial purposes vessels I and I2 may be built as sections of a single unitary apparatus having appropriate par titions. Preferably the mean inner diameter at the constrictions of member 6 is of the order of 0.6 to 1.0 cm., preferably proportional to the air flow rate as discussed hereinafter; and the mean inner diameter of the bulb or enlarged sections of member 6 is'from 25% to 100% greater than that of the constricted sections. Generally, the length of each constricted section in member 6 should be such as to provide a turbulent liquid body at least about 1 cm. deep, up to about 4 cm., preferably a total of at least 3 cm. of turbulent liquid through which the aerosol particles must pass. This turbulent mass has been found to be effective in facilitating the production of aerosol of the desirable uniformly small size. A possible "explanation may be the fact that the turbulence creates a myriad of liquid films through which the aerosol must pass, each of which assists in the production of the unique aerosols described herein as resulting from the use of the preferred conditions of my method and construction of my apparatus. The distance between the barriers in member G, i. e., the lengths of the enlargedpor- 4 tions, is not very critical, as long as the liquid barriers are maintained. The lower portion of member 6 may be set very closely over zone 2, but it is preferred that there be a distance of 3 to 4 cm. between the apertures of member 3 and the first liquid barrier constricted zone in member 6. Generally, the distance between the top of member 6 and the top of member I is in the range of 5 to 9 cm., preferably proportional to the air flow as described hereinafter.

In vessel I 2 the aerosol is preferably introduced at a depth in the range of 2 to 6 cm. below the liquid surface. The cross-sectional area at the surface of the liquid should be in the range of to 50 times that of the aerosol inlet tube, so as to provide a sudden decrease in Velocity of the aerosols.

The jet member may have one, two or three sets of air and liquid apertures, three being shown in the drawings.

In general, the size of the apertures may be such as to deliver an air flow per aperture in the range of 15 to 25 liters per minute, for conventional relatively low air'pressures of the order of '7 to 55 pounds per square inch gauge. For this air flow, the rate of dispersion of liquid per aperture is preferably 10 to 20 cc. per hour.

In a typical example, a 1% aqueous eosin solution is dispersed as aerosols of mean particle size of 0.43 micron, usingthe apparatus illustrated in Figure 1, and an air input of 28 pounds per square inch gauge. Substantially all the particles are less than 1 micron average diameter. The 'particle size of the aerosols is determined by passing the aerosols into a chamber, e. g., of 225 cubic meters capacity, the interior of which is maintained at atmospheric pressure. After dispersion for 10 minutes, the aerosols are allowed to settle on collector plates, coated with a thin film of petrolatum, e. g., for an hour, then the plates are protected by a. cover, cemented at the edges, e. g., with Duco cement, and immediately examined by means of an oil immersion microscope, e. g., 1125 magnification.

Alternatively, the particle size may be determined by nephelometric methods or by electron microscope means. .In the latter method, there are observed aerosol particles which are too small to be seen by means of the optical microscope, and when these are taken into consideration, the mean particle size of the aerosol will be even smaller (0.07 micron, mean size, as determined after collecting freezing and drying). a

Under similar conditions, a 10% aqueous solu tion of eosin gives aerosols having a mean particle size of 0.49 micron.

Similarresults are obtained using aqueous solutions of materials of different molecular weights. It is an advantage of the invention that, regardless of the type or molecular weight of the solute material or of the concentration thereof Within suitable therapeutic ranges, e. g., l to 10%, that aerosols of less than 0.5 micron mean diameter may be obtained, and most of these will fall within the range of 0.3 to 0.5 microns.

Passing the resulting aerosols from Vessel I2 into a second or serially into two more such vessels with distilled water therein did not show any color change. This indicates that liquid I3 just about completely removed all unstable eosin solution, red colored particles.

If desired, the vessel I2 and body of liquid I3 may be eliminated, in which case the particle size will vary with the concentration of the solute but will never e:gce ed0.8 micron (mean size) Al- IQEBGEOSQ ternatively, the vessel l2 may be used' bu-t' the body of liquid l-3 may be eliminated, inswhich case the-"particle size will vary-with the concentration of=the solutebut will never exceed 0.68 micron -(means size). These results indicate that the vessel 1 2 alone will remove some of the "larger particles, and that liquid 13 removes more ofthe larger-particles. I r Inthe-above examples,- thebody of liquid. [3 'in'vessl 1-2 is the same as'that of liquid5 in vessel I. "Other liquids may be used in vessel 1'3, e."-'g., alight mineral-oil, such as kerosene,-'aque- *ous solutionsofglyceroL-glycols or the'li-ke.

The particular jet --members discussed above are admirably adapted for producing aerosols. However, other types of jet members may be used,

' as known in the art, provided the resulting mist or cloud contains both very fine and stable liquid particles and also a substantial amount of larger relatively unstable particles. The unstable particles will tend to be removed in the turbulent liquid body, or in the treatments subsequent to contact with the turbulent body, or both. If desired, the liquid to be dispersed may be fed under positive pressure or at atmospheric pressure directly into tube 4, e. g., from an outside supply through suitable. connections, not shown. This prevents an increase in the concentration of the solution being dispersed during the dispersion.

A plurality of jet members and aerosol conduit members may be used, if desired.

If desired, the upper end of member 6 may be completely closed or partially closed, e. -g., by a stopper with a small opening, and very efiicient elimination of larger particles will result, but at a decreased rate of output.

The relatively uniform aerosols of very low mean particle size, having substantially all particles of less than 1 micron maximum size, are particularly suitable for use in aerosol therapy, especially in the treatment of the innermost passages or regions (alveoli) in the lungs. If it is desired to simultaneously treat or medicate the nasal or throat passages, larger mean particle size aerosols, having some particles of the order of l to 5 microns diameter, may be included. Such aerosols may be produced in the present apparatus by attaching member GB at the lower end of member 6 or 6A.

The aerosols produced in accordance with the invention may be suitable for other uses, e. g., precipitation or agglutination of very fine dust particles; which dust particles are so fine that they pass through a liquid layer, through the nasal and throat passages, and into the innermost regions of the lungs where they may deposit and produce very undesirable effects, e. g., silicosis. The very fine aerosol particles tend to agglomerate and coalesce with the very fine dust particles, to produce larger size individual particles and to produce dust aggregation which settle down more quickly and do not penetrate further than the upper respiratory passages.

In view of the foregoing disclosures, variations and modifications thereof will be apparent to those skilled in the art, and all such variations and modifications are broadly contemplated within the invention.

I claim:

1. In an apparatus for producing an improved aerosol, a vessel provided with atomizing means comprising a liquid feed tube in communication with a liquid supply and an upwardly directed air inlet tube, a conduit member having three -alternate constricted icrossesectional zones iset axially aboutvertically above said atomizing means-and adapted to assist' in forming: and supporting a turbulent liquid body, a hood mem'ber set around andover'said conduit member, said hood'member having a closed top and apertured sidewalls and said hood member dividing said vessel into two zones, and an aerosol outlet tube, the mean inner diameter at the constrictions of said conduit member, being in the'range of .0.6 to 1.0 cm. and the mean inner diameter of the enlarged sections of said conduitmember being in the range of 25 to greater than th diameter at the constrictions.

'2. In 'an apparatusfor-producing an improved aerosol, a vessel provided with a liquid reservoir, atomizing means comprising a liquid feed tube in communication with the said reservoir and an upwardly directed air inlet tube, a conduit member having three alternate constricted crosssectional zones set axially about vertically above said. atomizing means and adapted to assist in forming and supporting a turbulent liquid body, a hood member set around and over said conduit member, said hood member having a closed top and apertured sidewalls and said hood member dividing said vessel into two zones, means for introducing liquid on to the top of said hood member and liquid outlet means near the bottom of said hood member, and an aerosol outlet tube, the mean inner diameter of the constrictions of said conduit member being in the range of 0.6 to 1.0 cm. and the mean inner diameter of the enlarged sections of said conduit member being in the range of 25 to 100% greater than the diameter at the constrictions.

3. In an apparatus for producing an improved aerosol, a vessel provided with a liquid reservoir, atomizing means comprising a liquid feed tube in communication with the said reservoir and an upwardly directed air inlet tube, a conduit member having a plurality of alternate constricted cross-sectional zones set axially about vertically above said atomizing means and adapted to assist in forming and supporting a turbulent liquid body, a hood member set around and over said conduit member, said hood member having a closed top and apertured sidewalls and said hood member dividing said vessel into two zones, a tube member leading from the upper zone of said vessel to near the bottom of a liquid reservoir in a second vessel, and an aerosol outlet tube, the mean inner diameter at the constrictions of said conduit member being in the range of 0.6 to 1.0 cm. and the mean inner diameter of the enlarged sections of said conduit member being in the range of 25 to 100% greater than the diameter at the constrictions.

4. In an apparatus for producing an improved aerosol, a vessel provided with a liquid reservoir, atomizing means comprising a liquid feed tube in communication with the said reservoir and an upwardly directed air inlet tube, a conduit member having a plurality of alternate constricted cross-sectional zones set axially about vertically above said atomizing means and adapted to assist in forming and supporting a turbulent liquid body, a hood member set around and over said conduit member, said hood member having a closed top and apertured sidewalls and said hood member dividing said vessel into two zones, a tube member leading from the upper zone of said vessel to near the bottom of a liquid reservoir in a second vessel conical in form, and an aerosol outlet tube, the mean inner diameter at the con 7 strictions of said conduit member being in'the range of 0.6 to 1.0 cm. and the mean inner diameter of the enlarged sections of said conduit member being in the range of 25 to 100% greater than the diameter at the constrictions.- 5

LUCIEN DAUTREBANDE.

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